Tinengotinib
new
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 465967

CAS#: 2230490-29-4

Description: Tinengotinib, also known as TT-00420, is an antineoplastic tyrosine kinase inhibitor. Tinengotinib strongly inhibited Aurora A/B, FGFR1/2/3, VEGFRs, JAK1/2, and CSF1R in biochemical assays. Exposure to tinengotinib specifically inhibited proliferation across all subtypes of TNBC in vitro and in vivo, while leaving luminal breast cancer cells intact. Incubation of HCC1806 with tinengotinib led to dose-dependent downregulation of genes essential for TNBC cell growth and proliferation. Studies revealed that the potential mechanism of action of tinengotinib involved, predominantly, inhibition of Aurora A or B kinase activity, while inhibition of other pathways contributed to suppression of potency and activity. In vitro treatment of TNBC cell lines or in vivo administration in a syngeneic model with tinengotinib resulted in up-regulation of CXCL10 and 11 or diminished tumor-associated macrophage (TAM) infiltration.

Chemical Structure

img
Tinengotinib
CAS# 2230490-29-4
Instruction

Theoretical Analysis

MedKoo Cat#: 465967
Name: Tinengotinib
CAS#: 2230490-29-4
Chemical Formula: C20H19ClN6O
Exact Mass: 394.13
Molecular Weight: 394.863
Elemental Analysis: C, 60.84; H, 4.85; Cl, 8.98; N, 21.28; O, 4.05

Price and Availability

Size Price Availability Quantity
10mg USD 150 2 Weeks
25mg USD 250 2 Weeks
50mg USD 450 2 Weeks
100mg USD 750 2 Weeks
200mg USD 1250 2 Weeks
500mg USD 2950 2 Weeks
1g USD 4650 2 Weeks
2g USD 6950 2 Weeks
Bulk inquiry

Synonym: Tinengotinib; TT-00420; TT 00420; TT00420;

IUPAC/Chemical Name: 4-(5-(2-chlorophenyl)-3-methyl-1,10-dihydropyrazolo[4,3-b]pyrido[4,3-e][1,4]diazepin-8-yl)morpholine

InChi Key: DQFCVOOFMXEPOC-UHFFFAOYSA-N

InChi Code: InChI=1S/C20H19ClN6O/c1-12-18-20(26-25-12)23-16-10-17(27-6-8-28-9-7-27)22-11-14(16)19(24-18)13-4-2-3-5-15(13)21/h2-5,10-11H,6-9H2,1H3,(H2,23,25,26)

SMILES Code: CC1=NNC2=C1N=C(C3=CC=CC=C3Cl)C(C=NC(N4CCOCC4)=C5)=C5N2

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: To be determined

Shelf Life: >2 years if stored properly

Drug Formulation: To be determined

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Tinengotinib was found to have high permeability and high plasma protein binding and equally distributed between blood and plasma. There were no unique metabolites in human liver microsomes and tinengotinib showed moderate hepatic clearance. Tinengotinib is neither a potential inhibitor nor an inducer of P450 enzymes at clinically relevant concentrations, and unlikely to cause drug-drug interactions when used in combination with other drugs mediated by a key transporter, either as victim or perpetrator. Taken together, tinengotinib demonstrated a minimal risk of clinically relevant drug-drug interactions. Tinengotinib showed good oral bioavailability and dose-dependent exposures in both rat and dog after oral administration. The total radioactivity was largely distributed in the gastrointestinal system and liver, and tinengotinib could not easily pass through the blood-brain barrier. The major drug-related component in rat and dog plasma was unchanged drug (>89 %) with primary route of elimination via feces (>93 % of the dose) and minor via renal excretion (<4 % of the dose). Tinengotinib metabolism is mediated largely by CYP3A4, with minor contributions from CYP2D6 and CYP2C8. Major metabolic pathways include oxidation, oxidative cleavage of the morpholine ring, glucuronide and glutathione conjugations. The overall preclinical pharmacokinetics profile supported the selection and development of tinengotinib as a clinical candidate.

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 394.86 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
In vivo protocol:

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Ni S, Li L, Sun X, Wang Y, Yu Q, Wang W, Gu Z, Yu Z, Wu D, Wu F, Jiang S, Peng P. In vitro and in vivo pharmacokinetics, disposition, and drug-drug interaction potential of tinengotinib (TT-00420), a promising investigational drug for treatment of cholangiocarcinoma and other solid tumors. Eur J Pharm Sci. 2024 Jan 1;192:106658. doi: 10.1016/j.ejps.2023.106658. Epub 2023 Dec 2. PMID: 38048851.


2: Peng P, Qiang X, Li G, Li L, Ni S, Yu Q, Sourd L, Marangoni E, Hu C, Wang D, Wu D, Wu F. Tinengotinib (TT-00420), a Novel Spectrum-Selective Small-Molecule Kinase Inhibitor, Is Highly Active Against Triple-Negative Breast Cancer. Mol Cancer Ther. 2023 Feb 1;22(2):205-214. doi: 10.1158/1535-7163.MCT-22-0012. PMID: 36223547; PMCID: PMC9890131.